Background During anticoagulation for prevention of stroke in patients with non-valvular atrial fibrillation (NVAF), bleeding is the most serious complication. In Western countries, the incidences of major bleeding and intracranial hemorrhages with low-dose warfarin are known to occur at a rate of 0.4-1.3% and 0.2% per year, respectively. The purpose of this study was to investigate the incidence and risk factors for major bleeding related with warfarin therapy in Japanese patients with NVAF. Methods and Results From August 2004 to July 2005, 667 NVAF patients treated with warfarin for NVAF were followed-up. The target prothrombin time-international normalized ratio (PT-INR) value was set at 1.6-2.6 (low-dose warfarin). The exposure on warfarin was 503 patient-years (average PT-INR 2.00 ±0.40). During the follow-up period, 12 major bleeding complications occurred (2.38% per patient-year), which included 3 intracranial hemorrhages (0.60% per patient-year). Among the patients' characteristics, average PT-INR ≥2.27 during the study was identified as an independent risk factor for major bleeding. Conclusions The incidence of major bleeding and intracranial hemorrhages in Japanese NVAF patients with low-dose warfarin therapy was 2.38% and 0.60% per patient-year, respectively, which is higher than in Westerners. (Circ J 2007; 71: 761 - 765)